Cardiopulmonary bypass (CPB) and chemical arrest using cardioplegic solutions have traditionally provided surgeons with optimal operative conditions: hemodynamic control and cardiac quiescence. This optimal field has contributed to technical success in increasingly complex cardiac surgical operations. However, there has been recent interest in performing coronary artery bypass surgery without either cardiopulmonary bypass or cardioplegia. The quality of the distal anastomoses is a primary concern among cardiac surgeons who observe and perform coronary artery bypass graft procedures (CABG) unaided by cardiopulmonary bypass or cardioplegic arrest. Coronary artery bypass graft failure rate reported with off-pump coronary grafting range from 3.8–8.9%, while traditional CABG on CPB has a reported anastomotic failure rate of less than 1%. This may reflect a difference in anastomotic precision between off-pump CABG and CPB-aided CABG. Although the benefits of avoiding extra-corporeal circulation and global cardioplegia in beating heart procedures are important, they do not outweigh the performance of optimal coronary anastomoses.
The key difference in the anastomotic results between conventional CABG and off-pump CABG (OPCAB) is related to achieving elective asystole during construction of the distal anastomoses. Cardiac motion can be minimized during OPCAB procedures by inducing pharmacological bradycardia by administering beta adrenergic receptor blockers and mechanical stabilization by a variety of devices. Although these techniques improve operative conditions they only approximate the advantages of elective asystole that can be achieved with CPB and cardioplegia.
A state of Controlled Intermittent Asystole (CIA) would provide brief intervals of cardiac quiescence to facilitate placement of coronary anastomatic structures while avoiding the necessity of a cardiopulmonary bypass and cardioplegia. CIA would thus provide the surgeon with an important advantage otherwise gained only by full cardioplegic arrest on CPB. The CIA technique improves the precision of coronary anastomoses that would otherwise be performed on a beating heart and may reduce graft failure while increasing ease of operation, as described in application WO9909973, incorporated by reference herein in its entirety.
In particular, CIA can be achieved using unilateral (or bilateral) vagus nerve stimulation coupled with pharmacological potentiation of vagal impulses and pharmacological suppression of electromechanical escape activity. It has previously been demonstrated in WO 9817680, incorporated herein by reference in its entirety, that elective Controlled Intermittent Asystole is possible by vagus nerve stimulation after treatment with an acetylcholinesterase inhibitor, a beta-adrenergic receptor blocker, and a calcium channel blocker or combinations thereof. What is required, however, is an integrated system and apparatus that will provide optimal electrical pulses to the vagus nerve to induce cardiac arrest. The intermittent cardiac quiescent periods will be of sufficient duration to allow precise performance of surgical procedures that are not adversely interrupted by escape beats breaking through asystole. What are also required are electrostimulation devices that will permit the identification of the optimal position of an electrode or series of electrodes relative to a vagus nerve to induce asystole. What is further required are means and methods for applying the electric pulse to the nerve, either directly or indirectly and to administer a pharmaceutical composition to potentiate the influence of vagal stimulation on the heart rate, and prolong the period of asystole, thereby increasing the likelihood that the surgical procedure will proceed uninterrupted.
The present invention introduces apparatus, devices and methods that will allow the CIA technique to be performed with ease and precision.